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Molecular Biology, Pathobiology, and Genetics |
Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
Requests for reprints: Baolin Zhang, Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, 29 Lincoln Drive, Building 29A, Room 2B-24, Bethesda, MD 20892. Phone: 301-827-1784; Fax: 301-480-3256; E-mail: Baolin.zhang{at}fda.hhs.gov.
D4-GDI is a Rho GDP dissociation inhibitor that is widely expressed in hematopoietic cells. Its possible expression and function in breast cancer cells has not been described. Here, we found that D4-GDI is expressed in a panel of breast cancer cell lines, but not in benign-derived mammary epithelial cells. Knockdown of D4-GDI expression in MDA-MB-231 cells by RNA interference blocks cell motility and invasion. The cells lacking D4-GDI grown on Matrigel revert to a normal breast epithelial phenotype characterized by the formation of cavitary structures. Silencing D4-GDI expression inhibits ß1-integrin expression and cell-matrix adhesion. Reintroduction of D4-GDI fully restored both ß1-integrin expression and cellular invasion. Knockdown of D4-GDI in BT549 cells results in a similar effect. These results show that D4-GDI modulates breast cancer cell invasive activities. (Cancer Res 2006; 66(11): 5592-8)
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